Omission of intraoperative frozen section in sentinel lymph node biopsy for early breast cancer: impact on survival outcomes

Omission of intraoperative frozen section in sentinel lymph node biopsy for early breast cancer: impact on survival outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Omission of intraoperative frozen section in sentinel lymph node biopsy for early breast cancer: impact on survival outcomes Nattanan Treeratanapun, Bhoowit Lerttiendamrong, Voranaddha Vacharathit, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9454590/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background The implementation of sentinel lymph node biopsy (SLNB) with permanent section (PS) analysis alone in patients who satisfied the ACOSOG Z0011 criteria did not alter the standard of care offered by the additional frozen section (FS) analysis. This study reports the patient survival outcomes of early-stage breast cancer based on sentinel lymph node biopsy techniques. Methods Our previous investigation examined 453 SLNB cases at King Chulalongkorn Memorial Hospital, with follow-up concluding on April 15, 2025. The retrospective cohort study included patients diagnosed with clinically node-negative primary invasive breast cancer, who underwent breast-conserving surgery. The primary endpoint was 5-year disease-free survival (DFS), while secondary outcomes encompassed the overall cumulative incidence of local, distant, and axillary recurrence, as well as overall survival (OS). Results Of the 453 patients undergoing SLNB, 239 underwent SLNB with PS alone, while 214 received additional FS. Kaplan–Meier analysis demonstrated a statistically significant difference in DFS between groups (log-rank P = 0.008). In multivariable Cox regression analysis, with the FS group as the reference, the PS group showed a lower estimated risk of recurrence (hazard ratio 0.34; 95% CI 0.15–0.79). The 5-year DFS rates were 95.8% in the PS group and 93.5% in the FS group; however, this difference was not statistically significant when compared using crude event rates (P = 0.263). Overall survival was similar between groups (P = 0.596). In the PS group, local and distant recurrence rates were 1.3% and 2.5%, respectively, with no regional recurrences observed. Conclusion Based on the DFS and OS outcomes from our 5-year follow-up data, SLNB with PS analysis alone in patients meeting the ACOSOG Z0011 criteria was found to be comparable to SLNB with FS analysis. Permanent section PS Frozen section FS Early-stage breast cancer Sentinel lymph node biopsy SLNB ACOSOG Z0011 Figures Figure 1 Figure 2 Introduction Sentinel lymph node biopsy (SLNB) has become a cornerstone in staging and managing early-stage breast cancer patients with clinically negative nodes, allowing effective disease assessment while avoiding the morbidities of full axillary lymph node dissection (ALND) [ 1 , 2 ]. One of the main morbidities of axillary surgery is seroma formation, which remains an unresolved issue despite technological advances and adjunctive measures. This ongoing problem reinforces the rationale for axillary surgery de-escalation strategies, including sentinel lymph node biopsy and omission of axillary lymph node dissection in selected patients, as a more effective means of reducing seroma-related morbidity than technical modifications alone [ 3 – 5 ]. The landmark American College of Surgeons Oncology Group Z0011 trial (ACOSOG Z0011) demonstrated in 2017 that patients with one or two positive sentinel lymph nodes (SLNs) did not benefit from ALND in terms of overall or disease-free survival [ 6 ]. Recommendations from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) also support omission of completion ALND in patients meeting Z0011 criteria. In this setting, intraoperative evaluation of sentinel lymph nodes is unlikely to alter immediate surgical management and, therefore, is not routinely recommended when the results would not influence intraoperative decision-making [ 7 , 8 ]. SLN evaluation is conducted via two main histopathologic methods: intraoperative frozen section (FS) and postoperative permanent section (PS). Traditionally, FS allowed surgeons to perform immediate ALND if SLNs were found to be positive, thereby avoiding second surgeries [ 9 – 12 ]. However, following Z0011, the clinical utility of FS has been increasingly questioned. As Bishop et al. and Godazande et al. observed, FS usage has declined, especially when metastasis to more than two SLNs is uncommon [ 12 , 13 ]. Recent analyses have cast further doubt on FS utility by emphasizing its lower sensitivity and the potential for false negatives [ 14 , 15 ]. Recent studies, including those by Jung et al. and Wanis et al., have reported that omitting FS in patients undergoing breast conservative surgery (BCS) did not increase reoperation rates or worsen oncologic outcomes, aligning with updated guidelines recommending more conservative axillary management [ 16 , 17 ]. Multiple follow-up studies have shown that there were no differences in disease-free survival (DFS) and overall survival (OS) between those who underwent SLNB alone and those who received SLNB and ALND [ 6 , 18 , 19 ]. However, limited literature has assessed long-term survival based on the method of SLNB pathological analysis. At King Chulalongkorn Memorial Hospital, we previously conducted two retrospective studies evaluating the utility of intraoperative FS in early-stage breast cancer patients undergoing breast-conserving surgery [ 20 , 21 ]. These studies demonstrated that omitting FS did not significantly affect reoperation rates or short-term outcomes and that most patients with SLN metastases did not require further axillary intervention in accordance with ACOSOG Z0011 criteria. In addition, omission of intraoperative FS may offer practical advantages, including reduced operative time, lower healthcare costs, and improved operating room workflow efficiency. While our earlier work focused on immediate clinical endpoints, such as the need for second surgeries, long-term oncologic outcomes including DFS and OS have not been previously reported in this patient population. Therefore, this study serves as a 5-year follow-up of the same cohort of early-stage breast cancer patients who underwent SLNB with or without FS as part of BCS. The aim is to compare disease-free survival and overall survival between the FS and PS groups and to determine whether omitting intraoperative FS impacts long-term oncologic safety in this surgical context. Materials and Methods This retrospective study explored the five-year survival outcomes of patients with early-stage breast cancer after treatment with different SLNB techniques. The primary focus was to compare the disease-free survival (DFS) between the FS and PS groups. Overall survival (OS), recurrence at the local and regional levels, and distant metastases were also reported as secondary outcomes. We included all patients who underwent the SLNB procedure at KCMH from April 2016 to April 2021, with follow-up ending on April 15, 2025. The inclusion criteria were patients with early-stage breast cancer (T1 or T2) with clinically node-negative status who had undergone breast-conserving surgery and SLNB. Postoperative radiotherapy was recommended for all eligible patients in accordance with institutional protocols. However, not all patients received radiotherapy due to individual preferences, including concerns regarding potential side effects or personal beliefs. Patients who had received neoadjuvant chemotherapy and those with noninvasive breast cancer were excluded. A total of 453 SLNB cases were included, of which 239 underwent SLNB using PS alone and 214 underwent the FS technique (Fig. 1 ). Follow-up data were obtained through electronic medical record (EMR) review, including documentation from outpatient clinic visits, imaging studies, and pathology reports within our institution. Outcomes of interest included local recurrence, regional recurrence, distant metastasis, and survival. Events were identified based on clinical, radiological, or pathological confirmation recorded in the EMR. Patients without documented events were considered event-free at the time of last follow-up. Patients who were lost to follow-up were censored at the date of their last recorded clinical visit. Time-to-event outcomes were analyzed using standard survival analysis methods with right censoring. Missing data for baseline clinicopathological variables were minimal, and complete-case analysis was performed. No imputation methods were applied. Data on age, operation type, final pathological diagnosis, tumor staging classification, Nottingham histologic grading, lymphovascular invasion, HER-2 and hormonal receptor status and adjuvant treatment were extracted from medical records. Comparison of clinicopathological characteristics between patients with FS and those with PS was also performed. Clinical nodal status was evaluated through physical examination, whereas radiological nodal status was assessed via breast ultrasonography and mammography. SLNB was performed using isosulfan blue dye as a single-agent mapping tracer, which is the standard practice at the KCMH and throughout Thailand. All pathological diagnoses were based on the serial examination of sentinel lymph nodes (SLNs) using hematoxylin and eosin immunohistochemical staining. The study protocol was granted a waiver of informed consent owing to the retrospective design, minimal risk to participants, and the use of de-identified data. All data were handled in compliance with institutional data protection policies, and patient confidentiality was strictly preserved, with all identifiers removed prior to analysis. This study was conducted in accordance with the principle of the Declaration of Helsinki. The study protocol was reviewed and approved by the Institutional Review Board of Chulalongkorn University (COA No. 0985/2025). Statistical analysis Microsoft Excel 2019 was used to collect the data extracted from medical records. IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA) was utilized for conducting statistical analyses. Categorical data was reported as frequencies and percentages. Pearson Chi-square and Fisher exact tests were used to analyze the categorical variables. Disease-free survival (DFS) analysis was defined as the time from SLNB procedure to any event, including local breast cancer recurrences, axillary recurrences, distant metastases, and deaths from all causes. Overall survival (OS) analysis was defined as the time from SLNB procedure to deaths from any cause. Local breast cancer recurrence was defined as tumor recurrence in the breast, while regional recurrence referred to ipsilateral axillary recurrences. We employed the Kaplan-Meier method to estimate survival curves. The log-rank test was used to compare FS and PS survival. For the 5-year DFS, the noninferiority margin was established from the SLNB procedure to the time of event of interest was recorded. Time-to-event outcomes were analyzed using the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazards regression was used to explore factors associated with disease-free survival. The FS group was defined as the reference category. Covariates entered into the multivariable model were selected based on clinical relevance and baseline imbalance between groups, including surgical group (frozen section vs permanent section), lymphovascular invasion and HER2 status. Categorical variables were entered using indicator coding, with reference categories specified in the model output. Because this was a retrospective study with a limited number of events, the multivariable model was intended as an exploratory analysis. Formal proportional hazards diagnostics and extensive model optimization were limited by the small number of events. Categorical outcomes of crude event frequencies (e.g., number of recurrence events) were compared using chi-square or Fisher’s exact test (Table 2 ). Results A total of 453 SLNB cases that satisfied the inclusion criteria were included in this study. Two hundred and fourteen operations utilized intraoperative FS, while the remaining 239 operations underwent PS alone. The median (IQR) follow-up time was 5.3 (4.0-6.2) years in the FS group and 6.3 (5.1–6.5) years in the PS group. Patient age ranged from 26 to 89 years with a mean and median of 56.0 and 55.0 years, respectively. Comparison of clinicopathological features between patients in FS group and those in PS group are demonstrated in Table 1 . Seven types of histopathological diagnoses were found in this study: invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), ductal carcinoma in situ with micrometastasis (DCISM), mucinous carcinoma, papillary carcinoma, tubular carcinoma and mixed invasive breast carcinoma. IDC accounts for the majority of the histopathological diagnosis, accounting for 373 patients (82.3%). Presence of lymphovascular involvement was found in 93 (20.5%) patients. HER-2 immunohistochemistry status was reported as unknown in 36 cases, due to equivocal HER-2 status and lack of additional fluorescence in situ hybridization (FISH) test. The lack of additional FISH analysis was primarily attributable to patient financial constraints, as the cost of the test was not reimbursable in our healthcare system. Statistically significant differences of lymphovascular invasion status and HER-2 status were found between the FS and PS groups. No significant differences were identified between the FS and PS groups with respect to receipt of adjuvant chemotherapy, radiotherapy, targeted therapy, or in surgical margin status, indicating that the adjuvant treatment strategies and surgical quality outcomes were well-balanced across both cohorts. With respect to surgical margins, a total of 41 patients (9.1%) had positive margins at final pathology, comprising 18 patients (8.4%) in the FS group and 23 patients (9.6%) in the PS group (P = 0.653). Re-excision was performed in 6 patients in the FS group and 11 patients in the PS group. The majority of these cases were classified as focally involved margins. In such instances, patients were counseled regarding the risks and benefits of re-excision; however, most declined reoperation. Given that margin involvement was limited to focal disease, and that no statistically significant differences in margin positivity were observed between the FS and PS cohorts, these findings are unlikely to have affected the oncologic outcomes in either group. Table 1 Comparison of Clinicopathological Characteristics Between Patients Undergoing Frozen Section (FS) and Permanent Section alone (PS) Age Total (N = 453) FS group (N = 214) PS group (N = 239) p -value 0.205 ≤ 50 164 71 (43.3%) 93 (56.7%) >50 289 143 (49.5%) 146 (50.5%) Tumor size 0.628 pT1 (< 2 cm) 289 139 (48.1%) 150 (51.9%) pT2 (2–5 cm) 164 75 (45.7%) 89 (54.3%) Nodal status 1 pN0 392 180 (45.9%) 212 (54.1%) pN1 59 32 (54.2%) 27 (45.8%) pN2 2 2 (100%) 0 (0%) Histologic grade 0.489 1 101 53 (52.5%) 48 (47.5%) 2 243 111 (45.7%) 132 (54.3%) 3 109 50 (45.9%) 59 (54.1%) Histopathology 0.483 IDC 373 178 (47.7%) 195 (52.3%) ILC 24 15 (62.5%) 9 (37.5%) DCISM 22 7 (31.8%) 15 (68.2%) Mucinous 16 6 (37.5%) 10 (62.5%) Papillary 10 5 (50%) 5 (50%) Tubular 2 1 (50%) 1 (50%) Mixed 6 2 (33.3%) 4 (66.7%) Lymphovascular Invasion 0.035 Yes 93 53 (57.0%) 40 (43.0%) No 360 161 (44.7%) 199 (55.3%) Estrogen receptor 0.250 Positive 360 175 (48.6%) 185 (51.4%) Negative 93 39 (41.9%) 54 (58.1%) Progesterone Receptor 0.065 Positive 311 156 (50.2%) 155 (49.8%) Negative 142 58 (40.8%) 84 (59.2%) HER-2 0.002 Positive 84 35 (41.7%) 49 (58.3%) Negative 333 152 (45.6%) 181 (54.4%) Not known 36 27 (75.0%) 9 (25.0%) Adjuvant Hormonal Treatment 0.471 Yes 364 175 (48.1%) 189 (51.9%) No 89 39 (43.8%) 50 (56.2%) Adjuvant Chemotherapy 0.704 Yes 218 105 (48.2%) 113 (51.8%) No 235 109 (46.4%) 126 (53.6%) Adjuvant Radiotherapy 0.232 Yes 37 14 (37.8%) 23 (62.2%) No 416 200 (48.1%) 216 (51.9%) Targeted therapy 0.413 Yes 48 20 (41.7%) 28 (58.3%) No 405 194 (47.9%) 211 (52.1%) Margin 0.653 Positive 41 18 (43.9%) 23 (56.1%) Negative 412 196 (47.6%) 216 (52.4%) IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; DCISM, ductal carcinoma in situ with microinvasion; HER-2, human epidermal growth factor receptor 2, Statistically significant difference (p < 0.05). Overall, FS sensitivity and specificity for SLN metastasis were 95% and 100%, respectively. Regarding axillary management, four patients in the FS group underwent immediate ALND based on intraoperative findings, and one patient required delayed ALND due to a false-negative frozen section result. As for PS group, no patient in the PS-only cohort required delayed ALND, and no axillary reoperations were performed [ 20 , 21 ]. Kaplan–Meier analysis demonstrated a 5-year DFS of 93.5% in the FS group and 95.8% in the PS group. The difference was statistically significant in favor of the PS group (log-rank P = 0.008), with similarity confirmed (hazard ratio, 0.34; 95% CI, 0.15–0.79; P = 0.01; Fig. 2 A). FS was used as the reference category in the Cox model. Subgroups analyses stratified by lymphovascular invasion and HER2 status showed associations with disease recurrence (adjusted hazard ratio, 0.38; 95% confidence interval, 0.17–0.89; P = 0.026 and adjusted hazard ratio, 0.41; 95% confidence interval, 0.17–0.98; P = 0.045, respectively). On multivariable Cox proportional hazards regression, permanent section remained associated with favorable disease-free survival compared with frozen section. However, given the limited number of events, this adjusted analysis should be interpreted as exploratory. Overall, disease-free survival events occurred in 14 patients (6.5%) in the FS group and 10 patients (4.2%) in the PS group (P = 0.263). Overall survival was similar between the two groups. The 5-year OS did not differ significantly, with no survival disadvantage observed for the PS group compared to the FS group (log-rank P = 0.223; hazard ratio, 0.40; 95% CI, 0.09–1.83; P = 0.238; Fig. 2 B). A total of seven deaths were recorded: four patients (1.9%) in the FS group and three patients (1.3%) in the PS group, as summarized in Table 2 . As for Breast Cancer–Specific Survival (BCSS), among the seven deaths observed, only one was attributed to breast cancer, while the remaining six were due to non–cancer-related causes. This finding underscores the excellent BCSS in both cohorts. Note that the P-values in Table 2 reflect crude event-count comparisons and the P-values reported in the text reflect time-to-event (log-rank) analyses, which account for differences in follow-up time and censoring. Table 2 Summary of 5-year survival outcomes Local recurrences No. of event in FS group No. of event in PS group P - value 2 (0.9%) 3 (1.3%) 0.744 Regional recurrence 2 (0.9%) 0 (0.0%) 1 Distant metastases 8 (3.7%) 6 (2.5%) 0.451 Deaths from any cause 4 (1.9%) 3 (1.3%) 0.596 Disease-free survival 14 (6.5%) 10 (4.2%) 0.263 Values are represented as number and percentages. FS, frozen section; PS, permanent section; Statistically significant difference ( p < 0.05). Local recurrence occurred in 2 patients (0.9%) in the FS group and 3 patients (1.3%) in the PS group (P = 0.744). Regional axillary recurrence was observed in 2 patients (0.9%) in the FS group, with no events in the PS group. Distant metastases occurred in 8 patients (3.7%) in the FS group and 6 patients (2.5%) in the PS group (P = 0.451). Two patients in each group experienced both local recurrence and distant metastasis. Kaplan–Meier analysis revealed no significant difference in local recurrence (log-rank P = 0.672; Fig. 2 C). However, significant differences were observed in regional axillary recurrence (log-rank P = 0.030; Fig. 2 D) and distant metastases (log-rank P = 0.041; Fig. 2 E). Discussion In this 5-year retrospective cohort study involving 453 patients undergoing SLNB, we compared outcomes between intraoperative frozen section (FS) and permanent section (PS) analysis. Our results show that PS alone is comparable to FS in terms of disease-free survival (DFS) and overall survival (OS), aligning with earlier reports [ 6 , 22 ]. Specifically, the 5-year DFS was 95.8% in the PS group and 93.5% in the FS group, showing a statistically significant similarity to the PS method. In our analysis, we identified statistically significant differences in lymphovascular invasion (LVI) and HER-2 status between the FS and PS groups. Specifically, the FS group had a higher rate of LVI, while the PS group had a greater proportion of HER-2 positive tumors. Importantly, despite these differences, adjuvant treatment strategies including chemotherapy, endocrine therapy, radiotherapy, and HER-2–directed therapy were comparable between the two cohorts. Surgical quality indicators, such as margin status, were also balanced. As this was a retrospective cohort study rather than a randomized controlled trial, some degree of imbalance in baseline tumor biology was expected. Overall, these imbalances were minor and unlikely to have introduced significant bias into the survival results. A total of 37 of 453 patients (8.2%) did not receive radiotherapy. Although this represents a minority of the cohort, the proportion may appear relatively high and reflects real-world variation in treatment adherence, including patient preference and concerns regarding potential side effects. Since the 1980s, both mastectomy and breast-conserving surgery (BCS) with radiotherapy have been accepted as equivalent local treatments for early-stage breast cancer [ 23 ]. Recent studies further suggest that BCS with adjuvant radiotherapy may even offer improved survival over mastectomy [ 24 – 26 ]. Complementing surgical treatment, accurate axillary staging is critical for tailoring adjuvant therapy and optimizing outcomes. The ACOSOG Z0011 trial marked a paradigm shift in axillary management, concluding that SLNB alone is sufficient for patients with one or two metastatic SLNs undergoing BCS with radiation [ 6 ]. Follow-up studies confirmed that 10-year OS, DFS, and regional control were comparable between SLNB and ALND, with both arms exceeding 90% 5-year survival [ 19 , 27 – 28 ]. Several recent meta-analyses and reviews support our findings. A large 2023 meta-analysis by Bharath et al. confirmed that FS and touch imprint cytology offered lower diagnostic accuracy compared to PS, especially for micrometastases [ 15 ]. Similarly, Elshanbary et al. reported that FS had a sensitivity of only ~ 70%, and its omission did not significantly affect oncologic outcomes [ 29 ]. This mirrors the decline in FS use observed in major centers globally following ACOSOG Z0011[ 13 ]. The results also align with updated ASCO guidelines, which recommend against routine intraoperative evaluation of SLNs if patients meet Z0011 criteria (1,19). An interesting observation in our data was the slightly higher incidence of regional recurrences and distant metastases in the FS group, possibly attributable to selection bias. Although rare, late metastasis occurring beyond 8 years in the FS group raises questions about the long-term reliability of intraoperative assessments. This late recurrence trend was also observed by Cusimano et al. [ 30 ], suggesting the need for more extended follow-up in SLNB-based studies. When examining recurrence patterns, our study demonstrates that both local and regional events were exceedingly rare across both FS and PS groups. Local recurrence occurred in only 0.9% of FS patients and 1.3% of PS patients, showing no statistically significant difference, which mirrors the findings from ACOSOG Z0011, where omission of ALND did not increase locoregional recurrence at 10 years [ 6 , 31 ]. In our cohort, regional recurrence was observed only in the FS group (0.9%) and not in the PS group. Although this difference was not statistically significant due to the very low absolute event numbers, the pattern aligns with the consistently low axillary failure rates reported in Z0011. Importantly, our data confirm that intraoperative FS does not add measurable benefit in preventing axillary recurrences compared to PS alone. More recently, the INSEMA trial further advanced this concept by showing that even complete omission of SLNB in clinically and radiologically node-negative patients did not lead to excess regional recurrences when breast-conserving surgery and whole-breast irradiation were applied [ 32 ]. The long-held rationale for using FS has been to prevent second surgeries. However, concerns have been raised about the false negative rate of FS when compared to the final result, which varied from 9% to 33% [ 33 , 34 ]. Discordance of numbers of positive nodes reported by the intraoperative result and the permanent section have also been reported [ 35 ]. Previous studies at our center supports the claim that additional FS may not yield significant value in terms of reoperation prevented for early-stage breast cancer [ 20 , 21 , 36 ]. Our study found notable differences in DFS, regional recurrence, and distant metastases between both groups, with the FS group experiencing more events than the PS group. As evident from the Kaplan-Meier curve, it concluded that the standard care provided by PS alone is comparable to the FS technique in any event or survival outcome. Our findings also resonate with the evolving paradigm in axillary management, notably influenced by the SOUND (Sentinel node versus Observation after axillary UltraSound) trial. This randomized study demonstrated that in clinically node-negative patients (cT1N0) with negative axillary ultrasound, omission of SLNB did not compromise disease-free survival or overall survival, highlighting the potential of axillary ultrasound as a reliable tool for nodal staging [ 37 ]. Nevertheless, several limitations should be acknowledged. First, the trial initially excluded patients with higher-risk breast cancers, including those with high tumor grade, HER2-positive, or triple-negative subtypes, which limits its generalizability to modern practice. Second, some subsequent analyses applying the SOUND criteria have faced challenges with relatively small sample sizes and limited long-term follow-up, restricting conclusions on late recurrences or mortality. Third, the omission of SLNB eliminates pathological nodal information, which may influence adjuvant treatment decisions, such as chemotherapy or targeted therapy selection. Finally, the trial was registered relatively late and did not include early interim analyses, raising concerns regarding transparency of reporting [ 37 ]. It is also important to revisit the original rationale for performing intraoperative frozen section (FS) during SLNB. The purpose of FS was to avoid reoperation by allowing immediate completion axillary dissection if more than two positive sentinel nodes were detected. However, data show that the proportion of patients with ≥ 3 positive sentinel nodes is low (2–6%), limiting the practical yield of intraoperative FS to avert reoperation: e.g., only 6% had ≥ 3 positive SLNs in a large series and modern cohorts report about 2–3% [ 38 , 39 ]. As such, the clinical benefit of FS is limited. Moreover, intraoperative FS typically prolongs operative/anesthesia time and adds cost, whereas post-Z0011 era data show that reducing or omitting FS shortens operations and lowers costs without worsening outcomes, including in resource-limited settings [ 20 , 21 ]. Taken together, these considerations suggest that while the SOUND trial underscores the role of high-quality axillary imaging in reducing surgical interventions, the more practical and broadly applicable step in current practice is omission of intraoperative FS in well-selected, clinically and radiologically node-negative patients consistent with ACOSOG Z0011 criteria. The limitations of this study include the use of data from a single center with a limited sample size, which may affect the generalizability of the findings. As the data were extracted from real-world clinical practice, the lack of randomization between patients with and without FS introduces the potential for confounding factors. The number of recurrence events was low relative to the number of candidate covariates; therefore, the adjusted Cox model may have been vulnerable to overfitting, and these estimates should be interpreted as exploratory rather than definitive. Although our team made efforts to minimize loss to follow-up, we acknowledge that a small number of patients with incomplete follow-up may have influenced the results. Nevertheless, our findings suggest that omitting FS in favor of PS does not compromise oncologic safety and may streamline surgical workflows. Conclusions Omission of intraoperative frozen section in selected patients meeting with ACOSOG Z0011 criteria was not associated with worse oncologic outcomes. Despite baseline differences between groups, long-term disease-free survival and recurrence patterns were comparable. This approach is consistent with global trends and modern evidence-based practices, supporting de-escalation of axillary surgery without compromising oncologic safety. Declarations We would like to declare that generative AI (Chat GPT-3.5) was used solely for assistance in checking and refining the English language in this manuscript. The authors entirely generated the content, ideas, and findings presented in the manuscript without AI assistance. Conflicts of Interest : The authors declare the they have no competing interests. Disclosure statement This manuscript has been previously published in the research square preprint. Statement of Ethics The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study protocol was reviewed and approved by the Institutional review board of faculty of medicine, Chulalongkorn University on August 5, 2025, COA number: 0985/2025. Individual consent for this retrospective analysis was waived. Funding statement: No funding was available for this study. Author Contribution Nattanan Treeratanapun: Conceptualization, Data Curation, Validation, Formal analysis Investigation, Writing - Original Draft, Writing- Reviewing and Editing Bhoowit Lerttiendamrong: Conceptualization, Data Curation, Formal analysis, Investigation, Validation, Writing- Reviewing and Editing Voranaddha Vacharathit: Investigation , Writing- Reviewing and Editing Kasaya Tantiphlachiva: Investigation Phuphat Vongwattanakit: Investigation Sopark Manasnayakorn: Investigation Mawin Vongsaisuwon: Conceptualization, Methodology, Supervision, Validation, Writing - Review & Editing Acknowledgement The authors received no contribution in this study. 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Miltenburg DM, Miller C, Karamlou TB, Brunicardi FC. Meta-analysis of sentinel lymph node biopsy in breast cancer. J Surg Res. 1999;84(2):138–42. 10.1006/jsre.1999.5629 . Godazande G, Moradi S, Naghshvar F, Shojaee L. Is necessary intraoperative frozen section in sentinel lymph node biopsy for breast cancer patients? Asian Pac J Cancer Prev. 2020;21(3):647–51. 10.31557/APJCP.2020.21.3.647 . Bishop JA, Sun J, Ajkay N, Sanders MA. Decline in frozen section diagnosis for axillary sentinel lymph nodes as a result of the American College of Surgeons Oncology Group Z0011 trial. Arch Pathol Lab Med. 2016;140(8):830–5. 10.5858/arpa.2015-0296-OA . Elshanbary AA, et al. Diagnostic accuracy of intraoperative frozen section for sentinel lymph node metastasis. Environ Sci Pollut Res Int. 2022;29(32):48673–82. 10.1007/s11356-022-20569-4 . Bharath S, Sharma D, Yadav SK, Shekhar S, Jha CK. A Systematic Review and Meta-analysis of Touch Imprint Cytology and Frozen Section Biopsy and Their Comparison for Evaluation of Sentinel Lymph Node in Breast Cancer. World J Surg. 2023;47(2):478–88. 10.1007/s00268-022-06800-w . Wanis KN, Goetz L, So A, et al. The Prevalence of Sentinel Lymph Node Positivity and Implications for the Utility of Frozen Section Diagnosis Following Neoadjuvant Systemic Therapy in Patients with Clinically Node-Negative HER2-Positive or Triple-Negative Breast Cancer. Ann Surg Oncol. 2024;31(11):7339–46. 10.1245/s10434-024-15712-z . Jung SM, Woo J, Ryu JM, et al. Is the intraoperative frozen section analysis of sentinel lymph nodes necessary in clinically negative node breast cancer? Ann Surg Treat Res. 2020;99(5):251–8. 10.4174/astr.2020.99.5.251 . Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the ACOSOG Z0011 randomized trial. Ann Surg. 2010;252(3):426–32. 10.1097/SLA.0b013e3181f08f32 . Lee J, Choi JE, Kim SJ, et al. Comparative study between sentinel lymph node biopsy and axillary dissection in patients with one or two lymph node metastases. J Breast Cancer. 2018;21(3):306–14. 10.4048/jbc.2018.21.e44 . Treeratanapun N, Lerttiendamrong B, Vacharathit V, et al. Is sentinel lymph node biopsy without frozen section in early stage breast cancer sufficient in accordance with ACOSOG-Z0011? A retrospective review from King Chulalongkorn Memorial Hospital. BMC Surg. 2022;22(1):261. 10.1186/s12893-022-01709-6 . Lerttiendamrong B, Treeratanapun N, Vacharathit V, et al. Is routine intraoperative frozen section analysis of sentinel lymph nodes necessary in every early-stage breast cancer? Breast Cancer (Dove Med Press). 2022;14:281–90. 10.2147/BCTT.S380579 . Carleton N, et al. Outcomes after SLNB and radiotherapy in older women with early-stage breast cancer. JAMA Netw Open. 2021;4(4):e215388. 10.1001/jamanetworkopen.2021.5388 . Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233–41. 10.1056/NEJMoa022152 . Rajan KK, Fairhurst K, Birkbeck B, et al. Overall survival after mastectomy versus breast-conserving surgery with adjuvant radiotherapy for early-stage breast cancer: meta-analysis. BJS Open. 2024;8(3):zrae040. 10.1093/bjsopen/zrae040 . Christiansen P, Mele M, Bodilsen A, et al. Breast-conserving surgery or mastectomy? Impact on survival. Ann Surg Open. 2022;3(4):e205. 10.1097/AS9.0000000000000205 . Ji J, Yuan S, He J, et al. Breast-conserving therapy is associated with better survival than mastectomy in early-stage breast cancer: a propensity score analysis. Cancer Med. 2022;11(7):1646–58. 10.1002/cam4.4510 . Nayyar A, Strassle PD, Shen MR, et al. Survival analysis of early-stage breast cancer patients undergoing axillary lymph node dissection and sentinel lymph node dissection. Am J Surg. 2018;216(4):706–12. 10.1016/j.amjsurg.2018.07.027 . Huang TW, Su CM, Tam KW. Axillary management in women with early breast cancer and limited sentinel node metastasis: a systematic review and meta-analysis. Ann Surg Oncol. 2021;28:920–9. Elshanbary AA, et al. Diagnostic accuracy of intraoperative frozen section for sentinel lymph node metastasis. Environ Sci Pollut Res Int. 2022;29(32):48673–82. 10.1007/s11356-022-20569-4 . Cusimano MC, Vicus D, Pulman K, et al. Outcomes after sentinel lymph node biopsy and radiotherapy in older women with early-stage, ER-positive breast cancer. JAMA Netw Open. 2021;4(4):e215388. 10.1001/jamanetworkopen.2021.5388 . Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305(6):569–75. Reimer T, Stachs A, Veselinovic K, Kühn T, Heil J, Polata S, Marmé F, Müller T, Hildebrandt G, Krug D, Ataseven B, Reitsamer R, Ruth S, Denkert C, Bekes I, Zahm DM, Thill M, Golatta M, Holtschmidt J, Knauer M, Nekljudova V, Loibl S, Gerber B. Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial. N Engl J Med. 2025;392(11):1051–64. 10.1056/NEJMoa2412063 . Epub 2024 Dec 12. PMID: 39665649. Akay CL, Albarracin C, Torstenson T, et al. Factors impacting the accuracy of intra-operative evaluation of sentinel lymph nodes in breast cancer. Breast J. 2018;24(1):28–34. 10.1111/tbj.12829 . Francissen CM, van la Parra RF, Mulder AH, et al. Evaluation of the benefit of routine intraoperative frozen section analysis of sentinel lymph nodes in breast cancer. ISRN Oncol. 2013;2013:843793. 10.1155/2013/843793 . Geertsema D, Gobardhan PD, Madsen EV, et al. Discordance of intraoperative frozen section analysis with definitive histology of sentinel lymph nodes in breast cancer surgery. Ann Surg Oncol. 2010;17(10):2690–5. 10.1245/s10434-010-1052-x . Vongsaisuwon M, Vacharathit V, Lerttiendamrong B, et al. Reconsidering the role of frozen section in sentinel lymph node biopsy for mastectomy patients. J Surg Res. 2024;293:64–70. 10.1016/j.jss.2023.08.013 . Giannakou A, Kantor O, Park KU, Waks AG et al. Real-world implications of the SOUND trial. Ann Surg Oncol. 2024. Available from: https://link.springer.com/article/ 10.1245/s10434-024-16354-x Susini T, Nesi I, Renda I, Giani M, Nori J, Vanzi E, Bianchi S. Reducing the Use of Frozen Section for Sentinel Node Biopsy in Breast Carcinoma: Feasibility and Outcome. Anticancer Res. 2023;43(5):2161–70. 10.21873/anticanres.16378 . Yi M, Meric-Bernstam F, Ross MI, Akins JS, Hwang RF, Lucci A, Kuerer HM, Babiera GV, Gilcrease MZ, Hunt KK. How many sentinel lymph nodes are enough during sentinel lymph node dissection for breast cancer? Cancer. 2008;113(1):30–7. 10.1002/cncr.23514 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 06 May, 2026 Reviewers agreed at journal 06 May, 2026 Reviewers agreed at journal 06 May, 2026 Reviewers invited by journal 01 May, 2026 Editor assigned by journal 22 Apr, 2026 Submission checks completed at journal 20 Apr, 2026 First submitted to journal 18 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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SLNB, sentinel lymph node biopsy; PS, permanent section; FS, frozen section; BCT, breast-conserving therapy.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9454590/v1/5aa6821648015f0c3ac0da39.png"},{"id":109012250,"identity":"c5ae6097-73c3-4dc9-bfff-33d24f93f6d8","added_by":"auto","created_at":"2026-05-11 16:51:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2242816,"visible":true,"origin":"","legend":"\u003cp\u003eA-E. Kaplan Meier curve of Disease-Free Survival, Overall survival, Local Recurrences, Regional Recurrences, and Distant Metastases. SLNB, sentinel lymph node biopsy; PS, permanent section; FS, frozen section; BCT, breast-conserving therapy.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9454590/v1/77b719229411fa0680f57fd8.png"},{"id":109081426,"identity":"f5d625e6-f44d-4b45-86e4-4c289d328f9f","added_by":"auto","created_at":"2026-05-12 12:17:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2906954,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9454590/v1/abcb1afa-5a82-472c-85d1-ecbd4093f324.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Omission of intraoperative frozen section in sentinel lymph node biopsy for early breast cancer: impact on survival outcomes","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSentinel lymph node biopsy (SLNB) has become a cornerstone in staging and managing early-stage breast cancer patients with clinically negative nodes, allowing effective disease assessment while avoiding the morbidities of full axillary lymph node dissection (ALND) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. One of the main morbidities of axillary surgery is seroma formation, which remains an unresolved issue despite technological advances and adjunctive measures. This ongoing problem reinforces the rationale for axillary surgery de-escalation strategies, including sentinel lymph node biopsy and omission of axillary lymph node dissection in selected patients, as a more effective means of reducing seroma-related morbidity than technical modifications alone [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The landmark American College of Surgeons Oncology Group Z0011 trial (ACOSOG Z0011) demonstrated in 2017 that patients with one or two positive sentinel lymph nodes (SLNs) did not benefit from ALND in terms of overall or disease-free survival [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Recommendations from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) also support omission of completion ALND in patients meeting Z0011 criteria. In this setting, intraoperative evaluation of sentinel lymph nodes is unlikely to alter immediate surgical management and, therefore, is not routinely recommended when the results would not influence intraoperative decision-making [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. SLN evaluation is conducted via two main histopathologic methods: intraoperative frozen section (FS) and postoperative permanent section (PS). Traditionally, FS allowed surgeons to perform immediate ALND if SLNs were found to be positive, thereby avoiding second surgeries [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, following Z0011, the clinical utility of FS has been increasingly questioned. As Bishop et al. and Godazande et al. observed, FS usage has declined, especially when metastasis to more than two SLNs is uncommon [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Recent analyses have cast further doubt on FS utility by emphasizing its lower sensitivity and the potential for false negatives [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Recent studies, including those by Jung et al. and Wanis et al., have reported that omitting FS in patients undergoing breast conservative surgery (BCS) did not increase reoperation rates or worsen oncologic outcomes, aligning with updated guidelines recommending more conservative axillary management [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Multiple follow-up studies have shown that there were no differences in disease-free survival (DFS) and overall survival (OS) between those who underwent SLNB alone and those who received SLNB and ALND [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, limited literature has assessed long-term survival based on the method of SLNB pathological analysis.\u003c/p\u003e \u003cp\u003eAt King Chulalongkorn Memorial Hospital, we previously conducted two retrospective studies evaluating the utility of intraoperative FS in early-stage breast cancer patients undergoing breast-conserving surgery [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. These studies demonstrated that omitting FS did not significantly affect reoperation rates or short-term outcomes and that most patients with SLN metastases did not require further axillary intervention in accordance with ACOSOG Z0011 criteria. In addition, omission of intraoperative FS may offer practical advantages, including reduced operative time, lower healthcare costs, and improved operating room workflow efficiency. While our earlier work focused on immediate clinical endpoints, such as the need for second surgeries, long-term oncologic outcomes including DFS and OS have not been previously reported in this patient population. Therefore, this study serves as a 5-year follow-up of the same cohort of early-stage breast cancer patients who underwent SLNB with or without FS as part of BCS. The aim is to compare disease-free survival and overall survival between the FS and PS groups and to determine whether omitting intraoperative FS impacts long-term oncologic safety in this surgical context.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis retrospective study explored the five-year survival outcomes of patients with early-stage breast cancer after treatment with different SLNB techniques. The primary focus was to compare the disease-free survival (DFS) between the FS and PS groups. Overall survival (OS), recurrence at the local and regional levels, and distant metastases were also reported as secondary outcomes. We included all patients who underwent the SLNB procedure at KCMH from April 2016 to April 2021, with follow-up ending on April 15, 2025. The inclusion criteria were patients with early-stage breast cancer (T1 or T2) with clinically node-negative status who had undergone breast-conserving surgery and SLNB. Postoperative radiotherapy was recommended for all eligible patients in accordance with institutional protocols. However, not all patients received radiotherapy due to individual preferences, including concerns regarding potential side effects or personal beliefs. Patients who had received neoadjuvant chemotherapy and those with noninvasive breast cancer were excluded. A total of 453 SLNB cases were included, of which 239 underwent SLNB using PS alone and 214 underwent the FS technique (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFollow-up data were obtained through electronic medical record (EMR) review, including documentation from outpatient clinic visits, imaging studies, and pathology reports within our institution. Outcomes of interest included local recurrence, regional recurrence, distant metastasis, and survival. Events were identified based on clinical, radiological, or pathological confirmation recorded in the EMR. Patients without documented events were considered event-free at the time of last follow-up. Patients who were lost to follow-up were censored at the date of their last recorded clinical visit. Time-to-event outcomes were analyzed using standard survival analysis methods with right censoring. Missing data for baseline clinicopathological variables were minimal, and complete-case analysis was performed. No imputation methods were applied. Data on age, operation type, final pathological diagnosis, tumor staging classification, Nottingham histologic grading, lymphovascular invasion, HER-2 and hormonal receptor status and adjuvant treatment were extracted from medical records. Comparison of clinicopathological characteristics between patients with FS and those with PS was also performed. Clinical nodal status was evaluated through physical examination, whereas radiological nodal status was assessed via breast ultrasonography and mammography. SLNB was performed using isosulfan blue dye as a single-agent mapping tracer, which is the standard practice at the KCMH and throughout Thailand. All pathological diagnoses were based on the serial examination of sentinel lymph nodes (SLNs) using hematoxylin and eosin immunohistochemical staining. The study protocol was granted a waiver of informed consent owing to the retrospective design, minimal risk to participants, and the use of de-identified data. All data were handled in compliance with institutional data protection policies, and patient confidentiality was strictly preserved, with all identifiers removed prior to analysis. This study was conducted in accordance with the principle of the Declaration of Helsinki. The study protocol was reviewed and approved by the Institutional Review Board of Chulalongkorn University (COA No. 0985/2025).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eMicrosoft Excel 2019 was used to collect the data extracted from medical records. IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA) was utilized for conducting statistical analyses. Categorical data was reported as frequencies and percentages. Pearson Chi-square and Fisher exact tests were used to analyze the categorical variables. Disease-free survival (DFS) analysis was defined as the time from SLNB procedure to any event, including local breast cancer recurrences, axillary recurrences, distant metastases, and deaths from all causes. Overall survival (OS) analysis was defined as the time from SLNB procedure to deaths from any cause. Local breast cancer recurrence was defined as tumor recurrence in the breast, while regional recurrence referred to ipsilateral axillary recurrences. We employed the Kaplan-Meier method to estimate survival curves. The log-rank test was used to compare FS and PS survival. For the 5-year DFS, the noninferiority margin was established from the SLNB procedure to the time of event of interest was recorded. Time-to-event outcomes were analyzed using the Kaplan\u0026ndash;Meier method and compared with the log-rank test. Cox proportional hazards regression was used to explore factors associated with disease-free survival. The FS group was defined as the reference category. Covariates entered into the multivariable model were selected based on clinical relevance and baseline imbalance between groups, including surgical group (frozen section vs permanent section), lymphovascular invasion and HER2 status. Categorical variables were entered using indicator coding, with reference categories specified in the model output. Because this was a retrospective study with a limited number of events, the multivariable model was intended as an exploratory analysis. Formal proportional hazards diagnostics and extensive model optimization were limited by the small number of events. Categorical outcomes of crude event frequencies (e.g., number of recurrence events) were compared using chi-square or Fisher\u0026rsquo;s exact test (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 453 SLNB cases that satisfied the inclusion criteria were included in this study. Two hundred and fourteen operations utilized intraoperative FS, while the remaining 239 operations underwent PS alone. The median (IQR) follow-up time was 5.3 (4.0-6.2) years in the FS group and 6.3 (5.1\u0026ndash;6.5) years in the PS group. Patient age ranged from 26 to 89 years with a mean and median of 56.0 and 55.0 years, respectively. Comparison of clinicopathological features between patients in FS group and those in PS group are demonstrated in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Seven types of histopathological diagnoses were found in this study: invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), ductal carcinoma in situ with micrometastasis (DCISM), mucinous carcinoma, papillary carcinoma, tubular carcinoma and mixed invasive breast carcinoma. IDC accounts for the majority of the histopathological diagnosis, accounting for 373 patients (82.3%). Presence of lymphovascular involvement was found in 93 (20.5%) patients. HER-2 immunohistochemistry status was reported as unknown in 36 cases, due to equivocal HER-2 status and lack of additional fluorescence in situ hybridization (FISH) test. The lack of additional FISH analysis was primarily attributable to patient financial constraints, as the cost of the test was not reimbursable in our healthcare system. Statistically significant differences of lymphovascular invasion status and HER-2 status were found between the FS and PS groups. No significant differences were identified between the FS and PS groups with respect to receipt of adjuvant chemotherapy, radiotherapy, targeted therapy, or in surgical margin status, indicating that the adjuvant treatment strategies and surgical quality outcomes were well-balanced across both cohorts. With respect to surgical margins, a total of 41 patients (9.1%) had positive margins at final pathology, comprising 18 patients (8.4%) in the FS group and 23 patients (9.6%) in the PS group (P\u0026thinsp;=\u0026thinsp;0.653). Re-excision was performed in 6 patients in the FS group and 11 patients in the PS group. The majority of these cases were classified as focally involved margins. In such instances, patients were counseled regarding the risks and benefits of re-excision; however, most declined reoperation. Given that margin involvement was limited to focal disease, and that no statistically significant differences in margin positivity were observed between the FS and PS cohorts, these findings are unlikely to have affected the oncologic outcomes in either group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Clinicopathological Characteristics Between Patients Undergoing Frozen Section (FS) and Permanent Section alone (PS)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;453)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFS group (N\u0026thinsp;=\u0026thinsp;214)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePS group (N\u0026thinsp;=\u0026thinsp;239)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.205\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le; 50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 (43.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93 (56.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e289\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e143 (49.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e146 (50.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.628\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT1 (\u0026lt;\u0026thinsp;2 cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e289\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139 (48.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e150 (51.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT2 (2\u0026ndash;5 cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e89 (54.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNodal status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e392\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e180 (45.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e212 (54.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (54.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (45.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistologic grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.489\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (52.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (47.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e132 (54.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (45.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59 (54.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistopathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.483\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIDC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e178 (47.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e195 (52.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eILC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDCISM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (31.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (68.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucinous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePapillary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTubular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphovascular Invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (57.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (43.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e360\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e161 (44.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e199 (55.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEstrogen receptor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.250\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e360\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e185 (51.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (41.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54 (58.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgesterone Receptor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e156 (50.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e155 (49.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (40.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84 (59.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHER-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (58.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e152 (45.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e181 (54.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot known\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (75.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant Hormonal Treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.471\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175 (48.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e189 (51.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (43.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (56.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant Chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.704\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105 (48.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e113 (51.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e235\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e109 (46.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e126 (53.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (37.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (62.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e416\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200 (48.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e216 (51.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTargeted therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (58.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e405\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e194 (47.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e211 (52.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMargin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.653\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (43.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (56.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e412\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e196 (47.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e216 (52.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eIDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; DCISM, ductal carcinoma in situ with microinvasion; HER-2, human epidermal growth factor receptor 2, Statistically significant difference (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOverall, FS sensitivity and specificity for SLN metastasis were 95% and 100%, respectively. Regarding axillary management, four patients in the FS group underwent immediate ALND based on intraoperative findings, and one patient required delayed ALND due to a false-negative frozen section result. As for PS group, no patient in the PS-only cohort required delayed ALND, and no axillary reoperations were performed [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eKaplan\u0026ndash;Meier analysis demonstrated a 5-year DFS of 93.5% in the FS group and 95.8% in the PS group. The difference was statistically significant in favor of the PS group (log-rank P\u0026thinsp;=\u0026thinsp;0.008), with similarity confirmed (hazard ratio, 0.34; 95% CI, 0.15\u0026ndash;0.79; P\u0026thinsp;=\u0026thinsp;0.01; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). FS was used as the reference category in the Cox model. Subgroups analyses stratified by lymphovascular invasion and HER2 status showed associations with disease recurrence (adjusted hazard ratio, 0.38; 95% confidence interval, 0.17\u0026ndash;0.89; P\u0026thinsp;=\u0026thinsp;0.026 and adjusted hazard ratio, 0.41; 95% confidence interval, 0.17\u0026ndash;0.98; P\u0026thinsp;=\u0026thinsp;0.045, respectively). On multivariable Cox proportional hazards regression, permanent section remained associated with favorable disease-free survival compared with frozen section. However, given the limited number of events, this adjusted analysis should be interpreted as exploratory. Overall, disease-free survival events occurred in 14 patients (6.5%) in the FS group and 10 patients (4.2%) in the PS group (P\u0026thinsp;=\u0026thinsp;0.263). Overall survival was similar between the two groups. The 5-year OS did not differ significantly, with no survival disadvantage observed for the PS group compared to the FS group (log-rank P\u0026thinsp;=\u0026thinsp;0.223; hazard ratio, 0.40; 95% CI, 0.09\u0026ndash;1.83; P\u0026thinsp;=\u0026thinsp;0.238; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). A total of seven deaths were recorded: four patients (1.9%) in the FS group and three patients (1.3%) in the PS group, as summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e. As for Breast Cancer\u0026ndash;Specific Survival (BCSS), among the seven deaths observed, only one was attributed to breast cancer, while the remaining six were due to non\u0026ndash;cancer-related causes. This finding underscores the excellent BCSS in both cohorts. Note that the P-values in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e reflect crude event-count comparisons and the P-values reported in the text reflect time-to-event (log-rank) analyses, which account for differences in follow-up time and censoring.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of 5-year survival outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLocal recurrences\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. of event in FS group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo. of event in PS group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e- value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.9%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.3%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.744\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegional recurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistant metastases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (3.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.451\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeaths from any cause\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.596\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease-free survival\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.263\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eValues are represented as number and percentages.\u003c/p\u003e \u003cp\u003eFS, frozen section; PS, permanent section; Statistically significant difference (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\u003cp\u003eLocal recurrence occurred in 2 patients (0.9%) in the FS group and 3 patients (1.3%) in the PS group (P\u0026thinsp;=\u0026thinsp;0.744). Regional axillary recurrence was observed in 2 patients (0.9%) in the FS group, with no events in the PS group. Distant metastases occurred in 8 patients (3.7%) in the FS group and 6 patients (2.5%) in the PS group (P\u0026thinsp;=\u0026thinsp;0.451). Two patients in each group experienced both local recurrence and distant metastasis. Kaplan\u0026ndash;Meier analysis revealed no significant difference in local recurrence (log-rank P\u0026thinsp;=\u0026thinsp;0.672; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). However, significant differences were observed in regional axillary recurrence (log-rank P\u0026thinsp;=\u0026thinsp;0.030; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD) and distant metastases (log-rank P\u0026thinsp;=\u0026thinsp;0.041; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this 5-year retrospective cohort study involving 453 patients undergoing SLNB, we compared outcomes between intraoperative frozen section (FS) and permanent section (PS) analysis. Our results show that PS alone is comparable to FS in terms of disease-free survival (DFS) and overall survival (OS), aligning with earlier reports [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Specifically, the 5-year DFS was 95.8% in the PS group and 93.5% in the FS group, showing a statistically significant similarity to the PS method. In our analysis, we identified statistically significant differences in lymphovascular invasion (LVI) and HER-2 status between the FS and PS groups. Specifically, the FS group had a higher rate of LVI, while the PS group had a greater proportion of HER-2 positive tumors. Importantly, despite these differences, adjuvant treatment strategies including chemotherapy, endocrine therapy, radiotherapy, and HER-2\u0026ndash;directed therapy were comparable between the two cohorts. Surgical quality indicators, such as margin status, were also balanced. As this was a retrospective cohort study rather than a randomized controlled trial, some degree of imbalance in baseline tumor biology was expected. Overall, these imbalances were minor and unlikely to have introduced significant bias into the survival results. A total of 37 of 453 patients (8.2%) did not receive radiotherapy. Although this represents a minority of the cohort, the proportion may appear relatively high and reflects real-world variation in treatment adherence, including patient preference and concerns regarding potential side effects.\u003c/p\u003e \u003cp\u003eSince the 1980s, both mastectomy and breast-conserving surgery (BCS) with radiotherapy have been accepted as equivalent local treatments for early-stage breast cancer [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Recent studies further suggest that BCS with adjuvant radiotherapy may even offer improved survival over mastectomy [\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Complementing surgical treatment, accurate axillary staging is critical for tailoring adjuvant therapy and optimizing outcomes. The ACOSOG Z0011 trial marked a paradigm shift in axillary management, concluding that SLNB alone is sufficient for patients with one or two metastatic SLNs undergoing BCS with radiation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Follow-up studies confirmed that 10-year OS, DFS, and regional control were comparable between SLNB and ALND, with both arms exceeding 90% 5-year survival [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Several recent meta-analyses and reviews support our findings. A large 2023 meta-analysis by Bharath et al. confirmed that FS and touch imprint cytology offered lower diagnostic accuracy compared to PS, especially for micrometastases [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Similarly, Elshanbary et al. reported that FS had a sensitivity of only\u0026thinsp;~\u0026thinsp;70%, and its omission did not significantly affect oncologic outcomes [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. This mirrors the decline in FS use observed in major centers globally following ACOSOG Z0011[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The results also align with updated ASCO guidelines, which recommend against routine intraoperative evaluation of SLNs if patients meet Z0011 criteria (1,19). An interesting observation in our data was the slightly higher incidence of regional recurrences and distant metastases in the FS group, possibly attributable to selection bias. Although rare, late metastasis occurring beyond 8 years in the FS group raises questions about the long-term reliability of intraoperative assessments. This late recurrence trend was also observed by Cusimano et al. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], suggesting the need for more extended follow-up in SLNB-based studies.\u003c/p\u003e \u003cp\u003eWhen examining recurrence patterns, our study demonstrates that both local and regional events were exceedingly rare across both FS and PS groups. Local recurrence occurred in only 0.9% of FS patients and 1.3% of PS patients, showing no statistically significant difference, which mirrors the findings from ACOSOG Z0011, where omission of ALND did not increase locoregional recurrence at 10 years [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In our cohort, regional recurrence was observed only in the FS group (0.9%) and not in the PS group. Although this difference was not statistically significant due to the very low absolute event numbers, the pattern aligns with the consistently low axillary failure rates reported in Z0011. Importantly, our data confirm that intraoperative FS does not add measurable benefit in preventing axillary recurrences compared to PS alone. More recently, the INSEMA trial further advanced this concept by showing that even complete omission of SLNB in clinically and radiologically node-negative patients did not lead to excess regional recurrences when breast-conserving surgery and whole-breast irradiation were applied [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe long-held rationale for using FS has been to prevent second surgeries. However, concerns have been raised about the false negative rate of FS when compared to the final result, which varied from 9% to 33% [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Discordance of numbers of positive nodes reported by the intraoperative result and the permanent section have also been reported [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Previous studies at our center supports the claim that additional FS may not yield significant value in terms of reoperation prevented for early-stage breast cancer [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Our study found notable differences in DFS, regional recurrence, and distant metastases between both groups, with the FS group experiencing more events than the PS group. As evident from the Kaplan-Meier curve, it concluded that the standard care provided by PS alone is comparable to the FS technique in any event or survival outcome.\u003c/p\u003e \u003cp\u003eOur findings also resonate with the evolving paradigm in axillary management, notably influenced by the SOUND (Sentinel node versus Observation after axillary UltraSound) trial. This randomized study demonstrated that in clinically node-negative patients (cT1N0) with negative axillary ultrasound, omission of SLNB did not compromise disease-free survival or overall survival, highlighting the potential of axillary ultrasound as a reliable tool for nodal staging [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Nevertheless, several limitations should be acknowledged. First, the trial initially excluded patients with higher-risk breast cancers, including those with high tumor grade, HER2-positive, or triple-negative subtypes, which limits its generalizability to modern practice. Second, some subsequent analyses applying the SOUND criteria have faced challenges with relatively small sample sizes and limited long-term follow-up, restricting conclusions on late recurrences or mortality. Third, the omission of SLNB eliminates pathological nodal information, which may influence adjuvant treatment decisions, such as chemotherapy or targeted therapy selection. Finally, the trial was registered relatively late and did not include early interim analyses, raising concerns regarding transparency of reporting [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIt is also important to revisit the original rationale for performing intraoperative frozen section (FS) during SLNB. The purpose of FS was to avoid reoperation by allowing immediate completion axillary dissection if more than two positive sentinel nodes were detected. However, data show that the proportion of patients with \u0026ge;\u0026thinsp;3 positive sentinel nodes is low (2\u0026ndash;6%), limiting the practical yield of intraoperative FS to avert reoperation: e.g., only 6% had\u0026thinsp;\u0026ge;\u0026thinsp;3 positive SLNs in a large series and modern cohorts report about 2\u0026ndash;3% [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. As such, the clinical benefit of FS is limited. Moreover, intraoperative FS typically prolongs operative/anesthesia time and adds cost, whereas post-Z0011 era data show that reducing or omitting FS shortens operations and lowers costs without worsening outcomes, including in resource-limited settings [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Taken together, these considerations suggest that while the SOUND trial underscores the role of high-quality axillary imaging in reducing surgical interventions, the more practical and broadly applicable step in current practice is omission of intraoperative FS in well-selected, clinically and radiologically node-negative patients consistent with ACOSOG Z0011 criteria.\u003c/p\u003e \u003cp\u003eThe limitations of this study include the use of data from a single center with a limited sample size, which may affect the generalizability of the findings. As the data were extracted from real-world clinical practice, the lack of randomization between patients with and without FS introduces the potential for confounding factors. The number of recurrence events was low relative to the number of candidate covariates; therefore, the adjusted Cox model may have been vulnerable to overfitting, and these estimates should be interpreted as exploratory rather than definitive. Although our team made efforts to minimize loss to follow-up, we acknowledge that a small number of patients with incomplete follow-up may have influenced the results. Nevertheless, our findings suggest that omitting FS in favor of PS does not compromise oncologic safety and may streamline surgical workflows.\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003eOmission of intraoperative frozen section in selected patients meeting with ACOSOG Z0011 criteria was not associated with worse oncologic outcomes. Despite baseline differences between groups, long-term disease-free survival and recurrence patterns were comparable. This approach is consistent with global trends and modern evidence-based practices, supporting de-escalation of axillary surgery without compromising oncologic safety.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003eWe would like to declare that generative AI (Chat GPT-3.5) was used solely for assistance in checking and refining the English language in this manuscript. The authors entirely generated the content, ideas, and findings presented in the manuscript without AI assistance.\u003c/p\u003e\u003cp\u003e \u003ch2\u003e \u003cb\u003eConflicts of Interest\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eThe authors declare the they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eDisclosure statement\u003c/h2\u003e \u003cp\u003eThis manuscript has been previously published in the research square preprint.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eStatement of Ethics\u003c/h2\u003e \u003cp\u003eThe authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study protocol was reviewed and approved by the Institutional review board of faculty of medicine, Chulalongkorn University on August 5, 2025, COA number: 0985/2025. Individual consent for this retrospective analysis was waived.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding statement:\u003c/h2\u003e \u003cp\u003eNo funding was available for this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eNattanan Treeratanapun: Conceptualization, Data Curation, Validation, Formal analysis Investigation, Writing - Original Draft, Writing- Reviewing and Editing Bhoowit Lerttiendamrong: Conceptualization, Data Curation, Formal analysis, Investigation, Validation, Writing- Reviewing and Editing Voranaddha Vacharathit: Investigation , Writing- Reviewing and Editing Kasaya Tantiphlachiva: Investigation Phuphat Vongwattanakit: Investigation Sopark Manasnayakorn: Investigation Mawin Vongsaisuwon: Conceptualization, Methodology, Supervision, Validation, Writing - Review \u0026amp; Editing\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e \u003cp\u003eThe authors received no contribution in this study.\u003c/p\u003e\u003ch2\u003eData availability statement:\u003c/h2\u003e \u003cp\u003eThe Datasets generated and/or analyzed in the current study are not publicly available due to the individuals privacy issue but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLyman GH, Temin S, Edge SB et al. 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Cancer. 2008;113(1):30\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/cncr.23514\u003c/span\u003e\u003cspan address=\"10.1002/cncr.23514\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Permanent section, PS, Frozen section, FS, Early-stage breast cancer, Sentinel lymph node biopsy, SLNB, ACOSOG Z0011","lastPublishedDoi":"10.21203/rs.3.rs-9454590/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9454590/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe implementation of sentinel lymph node biopsy (SLNB) with permanent section (PS) analysis alone in patients who satisfied the ACOSOG Z0011 criteria did not alter the standard of care offered by the additional frozen section (FS) analysis. This study reports the patient survival outcomes of early-stage breast cancer based on sentinel lymph node biopsy techniques.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eOur previous investigation examined 453 SLNB cases at King Chulalongkorn Memorial Hospital, with follow-up concluding on April 15, 2025. The retrospective cohort study included patients diagnosed with clinically node-negative primary invasive breast cancer, who underwent breast-conserving surgery. The primary endpoint was 5-year disease-free survival (DFS), while secondary outcomes encompassed the overall cumulative incidence of local, distant, and axillary recurrence, as well as overall survival (OS).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 453 patients undergoing SLNB, 239 underwent SLNB with PS alone, while 214 received additional FS. Kaplan\u0026ndash;Meier analysis demonstrated a statistically significant difference in DFS between groups (log-rank P\u0026thinsp;=\u0026thinsp;0.008). In multivariable Cox regression analysis, with the FS group as the reference, the PS group showed a lower estimated risk of recurrence (hazard ratio 0.34; 95% CI 0.15\u0026ndash;0.79). The 5-year DFS rates were 95.8% in the PS group and 93.5% in the FS group; however, this difference was not statistically significant when compared using crude event rates (P\u0026thinsp;=\u0026thinsp;0.263). Overall survival was similar between groups (P\u0026thinsp;=\u0026thinsp;0.596). In the PS group, local and distant recurrence rates were 1.3% and 2.5%, respectively, with no regional recurrences observed.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eBased on the DFS and OS outcomes from our 5-year follow-up data, SLNB with PS analysis alone in patients meeting the ACOSOG Z0011 criteria was found to be comparable to SLNB with FS analysis.\u003c/p\u003e","manuscriptTitle":"Omission of intraoperative frozen section in sentinel lymph node biopsy for early breast cancer: impact on survival outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 16:51:16","doi":"10.21203/rs.3.rs-9454590/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-06T12:47:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"258321876863430119050358999531191769479","date":"2026-05-06T12:46:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"136140016933458279611422176569494371322","date":"2026-05-06T12:39:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-01T10:55:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-22T14:36:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-20T07:29:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Surgical Oncology","date":"2026-04-18T06:02:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3213d5cb-7c48-4c99-a396-b1c467602e1b","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-06T12:47:00+00:00","index":15,"fulltext":""},{"type":"reviewerAgreed","content":"258321876863430119050358999531191769479","date":"2026-05-06T12:46:51+00:00","index":14,"fulltext":""},{"type":"reviewerAgreed","content":"136140016933458279611422176569494371322","date":"2026-05-06T12:39:07+00:00","index":13,"fulltext":""},{"type":"reviewersInvited","content":"5","date":"2026-05-01T10:55:24+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T16:51:16+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 16:51:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9454590","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9454590","identity":"rs-9454590","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}